In percutaneous transluminal coronary angioplasty (PTCA), a balloon catheter is inserted through a brachial or femoral artery, positioned across a coronary artery occlusion, and inflated to compress against atherosclerotic plaque to open, by remodeling, the lumen of the coronary artery. The balloon is then deflated and withdrawn. Problems with PTCA include formation of intimal flaps or torn arterial linings, both of which can create another occlusion in the lumen of the coronary artery. Moreover, thrombosis and restenosis may occur several months after the procedure and create a need for additional angioplasty or a surgical bypass operation. Stents are used to address these issues. Stents are small, intricate, implantable medical devices and are generally left implanted within the patient to reduce occlusions, inhibit thrombosis and restenosis, and maintain patency within vascular lumens such as, for example, the lumen of a coronary artery.
The treatment of a diseased site or lesion with a stent involves both delivery and deployment of the stent. Stent delivery refers to introducing and transporting the stent through an anatomical lumen to a desired treatment site, such as a lesion in a vessel. An anatomical lumen can be any cavity, duct, or a tubular organ such as a blood vessel, urinary tract, and bile duct. Stent deployment corresponds to expansion of the stent within the anatomical lumen at the region requiring treatment. Delivery and deployment of a stent are accomplished by positioning the stent about one end of a catheter, inserting the end of the catheter through the skin into an anatomical lumen, advancing the catheter in the anatomical lumen to a desired treatment location, expanding the stent at the treatment location, and removing the catheter from the lumen with the stent remaining at the treatment location.
In the case of a balloon expandable stent, the stent is mounted about a balloon disposed on the catheter. Mounting the stent typically involves compressing or crimping the stent onto the balloon prior to insertion in an anatomical lumen. At the treatment site within the lumen, the stent is expanded by inflating the balloon. The balloon may then be deflated and the catheter withdrawn from the stent and the lumen, leaving the stent at the treatment site. In the case of a self-expanding stent, the stent may be secured to the catheter via a retractable sheath. When the stent is at the treatment site, the sheath may be withdrawn which allows the stent to self-expand.
Stents are often modified to provide drug delivery capabilities to further address thrombosis and restenosis. Stents may be coated with a polymeric carrier impregnated with a drug or therapeutic substance. A conventional method of coating includes applying a composition including a solvent, a polymer dissolved in the solvent, and a therapeutic substance dispersed in the blend to the stent by immersing the stent in the composition or by spraying the composition onto the stent. The solvent is allowed to evaporate, leaving on the stent strut surfaces a coating of the polymer and the therapeutic substance impregnated in the polymer.
The application of a uniform coating with good adhesion to a substrate can be difficult for small and intricate medical devices, such as certain stents for coronary and peripheral arteries. Such stents can be quite small. Stents for the coronary vessel anatomy typically have an overall diameter of only a few millimeters and a total length of several millimeters to tens of millimeters. Stents for the peripheral vessel anatomy are generally greater in diameter and length. Such peripheral stents may have a diameter up to 10 mm and a length of up to a few hundred millimeters. These stents may be constructed of a fine mesh network of struts, which provide support or push against the walls of the anatomical lumen in which the stent is implanted.
Conventional drug eluting stents have a drug coating that covers all surfaces of the stent strut, referred to as a conformal drug coating. With a conformal drug coating, the abluminal, luminal, and side surfaces of the strut release the drug. Abluminal surfaces face toward and contact the anatomical tissue, such as a blood vessel wall. Luminal surfaces face toward the center of the anatomical lumen and make contact with fluids in the anatomical lumen. Other drug eluting stents include depots or pockets with openings on the abluminal and/or luminal surfaces of the stent strut. With these types of drug eluting stents there are concerns with uniformity of the drug concentration generated within the patient. In general, drug concentration should be kept at a level that provides therapeutic effect and avoids or minimizes toxicity.
One study has shown that the drug concentration generated from conventional stents having a conformal drug coating varies significantly across the stent. For some stent strut patterns after a few days from implantation, drug concentration variability corresponding to plus and minus two standard deviations was found to be 3.3×0−5±2.4×10−5 kg/m3. This gives a drug concentration range of 0.9×10−5 to 5.7×10−5 kg/m3, which is about a factor of six. This very wide range can be acceptable for some drugs which have a wide therapeutic window (i.e., provide a therapeutic effect without toxicity over a wide concentration). However, this very wide range is of concern for drugs with relatively higher toxicity such as paclitaxel.
Accordingly, there is a continuing need for an implantable prosthesis and method of intraluminal drug delivery with improved drug concentration uniformity.